Neocortical plasticity is not usually associated with changes in reproductive function. However, we have shown a six to 10-fold increase in the number of astrocytes labeled with glial fibrillary acidic protein (GFAP) and astrocytic basic fibroblast growth factor or FGF-2 (bFGF) in the cingulate cortex area 2 (Cg2) in postpartum rats, indicative of changes in connectivity in this area. In the present studies, we investigated the necessary and sufficient stimuli for these changes to occur. We show that 3 h of maternal experience combined with a hormonal treatment that mimics late pregnancy induces the astrocytic changes in Cg2 in virgin rats. The extent of these changes was similar to those of postpartum females. Sensitized virgin females did not show any astrocytic changes after 3 h of maternal behavior, suggesting that a similar amount of maternal experience alone is not sufficient to increase astrocytic bFGF- and GFAP-immunoreactivity in Cg2. Consistent with these data, eliminating early maternal experience by removing pups immediately postpartum abolishes the increased bFGF and GFAP protein expression in the cingulate cortex. These results suggest that maternal experience and hormonal state interact to produce astrocytic remodeling in the Cg2. The current results are consistent with a role for the cingulate cortex in maternal responsivity as suggested by early lesion studies in rats and more recent imaging studies in humans.

Satellite glial cells (SGCs) surrounding primary sensory neurons are similar to astrocytes of the central nervous system in that they buffer the extracellular environment via potassium and calcium channels and express the intermediate filament glial fibrillary acidic protein (GFAP). Peripheral nerve injury induces a reactive state in SGCs that includes SGC proliferation, increased SGC/SGC coupling via gap junctions, decreased inward rectifying potassium channel 4.1 (Kir 4.1) expression and increased expression of GFAP and the common neurotrophin receptor, p75NTR. In contrast, neuronal p75NTR expression, normally detected in ∼80% of adult rat sensory neurons, decreases in response to peripheral axotomy. Given the differential regulation of p75NTR expression in neurons versus SGCs with injury, we hypothesized that reduced signaling via neuronal p75NTR contributes to the induction of a reactive state in SGCs. We found that reducing neuronal p75NTR protein expression in uninjured sensory neurons by intrathecal subarachnoid infusion of p75NTR-selective anti-sense oligodeoxynucleotides for one week was sufficient to induce a "reactive-like" state in the perineuronal SGCs akin to that normally observed following peripheral nerve injury. This reactive state included significantly increased SGC p75NTR, GFAP and gap junction protein connexin-43 protein expression, increased numbers of SGCs surrounding individual sensory neurons and decreased SGC Kir 4.1 channel expression. Collectively, this supports the tenet that reductions in target-derived trophic support leading to, or as a consequence of, reduced neuronal p75NTR expression plays a critical role in switching the SGC to a reactive state.

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